Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/117867
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Type: Journal article
Title: Synergy between nutritional immunity and independent host defenses contributes to the importance of the MntABC manganese transporter during Staphylococcus aureus infection
Author: Radin, J.R.
Zhu, J.
Brazel, E.
McDevitt, C.
Kehl-Fie, T.E.
Citation: Infection and Immunity, 2019; 87(1):1-14
Publisher: American Society for Microbiology
Issue Date: 2019
ISSN: 0019-9567
1098-5522
Statement of
Responsibility: 
Jana N. Radin, Jamie Zhu, Erin B. Brazel, Christopher A. McDevitt, Thomas E. Kehl-Fie
Abstract: During infection, the host utilizes a diverse array of processes to combat invaders, including the restriction of availability of essential nutrients such as manganese. Similarly to many other pathogens, Staphylococcus aureus possesses two manganese importers, MntH and MntABC. Several infection models have revealed a critical role for MntABC during staphylococcal infection. However, culture-based studies have suggested parity between the two transporters when cells are resisting manganese starvation imposed by the manganese binding immune effector calprotectin. In this investigation, initial elemental analysis revealed that MntABC is the primary transporter responsible for obtaining manganese in culture in the presence of calprotectin. MntABC was also necessary to maintain wild-type levels of manganese-dependent superoxide dismutase activity in the presence of calprotectin. Building on this framework, we investigated if MntABC enabled S. aureus to resist the synergistic actions of nutritional immunity and other host defenses. This analysis revealed that MntABC critically contributes to staphylococcal growth when S. aureus is subjected to manganese limitations and exposed to oxidative stress. This transporter was also important for growth in manganese-limited environments when S. aureus was forced to consume glucose as an energy source, which occurs when it encounters nitric oxide. MntABC also expanded the pH range conducive for S. aureus growth under conditions of manganese scarcity. Collectively, the data presented in this work provide a robust molecular basis for the crucial role of MntABC in staphylococcal virulence. Further, this work highlights the importance of synergy between host defenses and the necessity of evaluating the contribution of virulence factors to pathogenesis in the presence of multiple stressors.
Keywords: ABC transporters; calprotectin; infection; manganese; MntABC; MntH; nutritional immunity; Staphylococcus aureus
Rights: Copyright © 2018 American Society for Microbiology. All Rights Reserved.
RMID: 0030101937
DOI: 10.1128/IAI.00642-18
Grant ID: http://purl.org/au-research/grants/nhmrc/1122582
http://purl.org/au-research/grants/nhmrc/1140554
http://purl.org/au-research/grants/arc/DP170102102
http://purl.org/au-research/grants/arc/FT170100006
Appears in Collections:Microbiology and Immunology publications

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